SGLT1-Mediated Glucose Uptake in Jejunum: Diurnal Rhythm in Intestinal Function
Anita Balakrishnan*1, Ali Tavakkolizadeh1, ADAM Stearns1, Jan Rounds1, Michael Giuffrida1, Jennifer L. Irani1, David Rhoads2, Stanley W. Ashley1
1Surgery, Brigham and Women's Hospital, Boston, MA; 2Department of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA
Background:Diurnal rhythms of gene and protein expression of apical Na+/glucose transporter (SGLT1) in jejunum are well-described. We now examine SGLT1 at the functional level. Also, we tested whether rhythmic expression of Sglt1 transcription factors Hepatocyte Nuclear Factors (HNF)1α and β could contribute to the SGLT1 rhythm.
Methods:Everted sleeves were used to determine phloridzin-sensitive glucose uptake in rat jejunum at ZT3, ZT9, ZT15 and ZT21 (Lights-on is ZT0; n=8 per time). Sglt1 and Hnf1 mRNA levels were measured from jejunal mucosa using quantitative PCR and analyzed with ANOVA.
Results:Sglt1 mRNA was significantly higher at ZT9 compared to ZT3 or ZT21 (p<0.001). Phloridzin-sensitive glucose uptake was significantly higher at ZT15 (p<0.05 vs. ZT3, Fig.1 ). No temporal changes in Hnf1a or 1b mRNA levels were detected.
Discussion: Intestinal glucose uptake varies diurnally, peaking during maximal nutrient delivery and preceded by an anticipatory increase mRNA. Absence of changes in Hnf1a or 1b mRNA suggests the involvement of downstream regulatory mechanisms, e.g., HNF1 heterodimer formation or phosphorylation. Understanding the underlying mechanisms will help identify novel approaches to therapeutic modulation of intestinal function.
2007 Program and Abstracts | 2007 Posters